Medtronic Critic Raises Infuse Cancer Alarm

A prominent medical researcher and critic of Medtronic Inc. has warned that the association between its Infuse bone growth product and cancer might be stronger than originally thought. Dr. Eugene Carragee, a Stanford University School of Medicine professor and editor-in-chief of the Spine Journal, says his research indicated patients who received recombinant bone morphogenetic protein-2, or rhBMP-2, were three to five times more likely to develop cancer within a few years of implantation.

RhBMP-2 is the bone growth protein found in Medtronic’s Infuse bone graft. It was also used in a higher dose in Medtronic’s Amplify product, which was rejected by the U.S. Food & Drug Administration (FDA) in March because of a link to cancer.

Yesterday, during a presentation at the annual North American Spine Society meeting in Chicago on Thursday, Carragee said an analysis he performed of a Medtronic clinical trial raised serious concerns about a cancer risk posed by rhBMP-2. According to a report from the Milwaukee Journal-Sentinel, that study involved 239 patients who got the high-dose Amplify product and 224 who got a conventional graft of their own hip bone. At roughly three-year follow-up, 5% of those who got Amplify were diagnosed with a new cancer, compared with 1.3% who got the hip bone graft. After two to three years of follow-up, Amplify patients were four to five times more likely to develop at least one new malignancy.

The Amplify study was published in 2009, but the authors, who had received millions from Medtronic in royalties for other products, never mentioned the cancer cases in their article. The cancer cases were only noted in an accompanying table, the Journal-Sentinel said.

In an interview with The New York Times, Carragee said the cancer findings could have serious implications for people receiving Infuse. Doctors often administer Infuse off-label at levels significantly above the recommended dosages, ones that approach or exceed the amount of rhBMP-2 found in a dose of Amplify, he said. Carragee also voiced particular concern about the use of Infuse in certain patients like smokers or those with genetic factors that put them at higher risk for cancer, the Times said.

This isn’t the first time Carragee has raised questions about Medtronic-sponsored research for rhBMP-2. This past June, a Spine Journal article authored by Carragee reported that Medtronic-paid surgeons had failed to report serious complications from Infuse, including cancer, sterility in men, infections, bone dissolution and worsened back and leg pain. The article said complications occurred in 10 to 50 percent of patients who got the product in 13 Medtronic-funded clinical trials between 2000 and 2010. The scandal that article sparked prompted Medtronic to commission researchers at Yale to conduct a review of its Infuse clinical trials, and their report is expected to be completed next year.

Infuse was approved by the FDA in 2002. In July 2008, the agency warned that the use of Infuse Bone Graft and similar products had caused serious problems when they were used off-label in cervical spine (neck) surgeries.

The U.S. Senate Finance Committee has been investigating Infuse for several years, and recently â€“ thanks to Carrageeâ€™s Spine Journal article â€“ demanded Medtronic turn over records detailing payments made to Infuse researchers. Meanwhile, the U.S. Justice Department is investigating off-label use of Infuse.